Home LiteratureArticle Details
PMID: 7712513 Published · ppublish English Journal Article Review

Tetrodotoxin-resistant sodium channels.

Cellular and molecular neurobiology ·Vol. 14 ·No. 3 ·1994-06-00 ·Pages 227-44

Yoshida S

Abstract

1. Tetrodotoxin (TTX) has been widely used as a chemical tool for blocking Na+ channels. However, reports are accumulating that some Na+ channels are resistant to TTX in various tissues and in different animal species. Studying the sensitivity of Na+ channels to TTX may provide us with an insight into the evolution of Na+ channels. 2. Na+ channels present in TTX-carrying animals such as pufferfish and some types of shellfish, frogs, salamanders, octopuses, etc., are resistant to TTX. 3. Denervation converts TTX-sensitive Na+ channels to TTX-resistant ones in skeletal muscle cells, i.e., reverting-back phenomenon. Also, undifferentiated skeletal muscle cells contain TTX-resistant Na+ channels. Cardiac muscle cells and some types of smooth muscle cells are considerably insensitive to TTX. 4. TTX-resistant Na+ channels have been found in cell bodies of many peripheral nervous system (PNS) neurons in both immature and mature animals. However, TTX-resistant Na+ channels have been reported in only a few types of central nervous system (CNS). Axons of PNS and CNS neurons are sensitive to TTX. However, some glial cells have TTX-resistant Na+ channels. 5. Properties of TTX-sensitive and TTX-resistant Na+ channels are different. Like Ca2+ channels, TTX-resistant Na+ channels can be blocked by inorganic (Co2+, Mn2+, Ni2+, Cd2+, Zn2+, La3+) and organic (D-600) Ca2+ channel blockers. Usually, TTX-resistant Na+ channels show smaller single-channel conductance, slower kinetics, and a more positive current-voltage relation than TTX-sensitive ones. 6. Molecular aspects of the TTX-resistant Na+ channel have been described. The structure of the channel has been revealed, and changing its amino acid(s) alters the sensitivity of the Na+ channel to TTX. 7. TTX-sensitive Na+ channels seem to be used preferentially in differentiated cells and in higher animals instead of TTX-resistant Na+ channels for rapid and effective processing of information. 8. Possible evolution courses for Na+ and Ca2+ channels are discussed with regard to ontogenesis and phylogenesis.

MeSH Terms
Animals Biological Evolution Calcium Channel Blockers/pharmacology Embryonic and Fetal Development Kinetics Muscles/drug effects,metabolism Neuroglia/drug effects,metabolism Neurons/drug effects,metabolism Sodium Channels/drug effects,metabolism Tetrodotoxin/pharmacology
Chemicals
Calcium Channel Blockers Sodium Channels Tetrodotoxin
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Yoshida S
Department of Physiology, Fukui Medical School, Japan.
References (119)
119 references, click to expand
  1. Action potential generation in denervated rat skeletal muscle. II. The action of tetrodotoxin.
    Acta Physiol Scand. 1971 May;82(1):70-8 PMID: 4327036
  2. The reduction of calcium current associated with early differentiation of the murine embryo.
    J Physiol. 1985 Jun;363:71-86 PMID: 2410611
  3. Permeation of divalent and monovalent cations through the ovarian oocyte membrane of the mouse.
    J Physiol. 1983 Jun;339:631-42 PMID: 6310091
  4. Changes in membrane properties of chick embryonic hearts during development.
    J Gen Physiol. 1972 Oct;60(4):430-53 PMID: 4263008
  5. Responses dependent on alkaline earth cations (Ca, Sr, Ba) in dorsal root ganglion cells of the adult mouse.
    Brain Res. 1980 Apr 28;188(2):593-7 PMID: 7370779
  6. Chemical modification reduces the conductance of sodium channels in nerve.
    Nature. 1980 Jan 17;283(5744):293-5 PMID: 6965422
  7. Resistance to tetrodotoxin and saxitoxin in nerves of bivalve molluscs. A possible correlation with paralytic shellfish poisoning.
    Toxicon. 1972 May;10(3):273-8 PMID: 5072092
  8. Glial and neuronal forms of the voltage-dependent sodium channel: characteristics and cell-type distribution.
    Neuron. 1989 Apr;2(4):1375-88 PMID: 2560639
  9. SkM2, a Na+ channel cDNA clone from denervated skeletal muscle, encodes a tetrodotoxin-insensitive Na+ channel.
    Mol Pharmacol. 1991 May;39(5):604-8 PMID: 1851958
  10. Sodium and calcium currents of acutely isolated adult rat superior cervical ganglion neurons.
    Pflugers Arch. 1988 May;411(5):481-90 PMID: 3387185
  11. A heart-like Na+ current in the medial entorhinal cortex.
    Neuron. 1993 Dec;11(6):1037-47 PMID: 8274275
  12. Na+ current kinetics are not the determinants of the action potential duration in neurons of the rat ventral tegmental area.
    Brain Res Bull. 1992 Nov;29(5):691-5 PMID: 1330219
  13. Slow inactivation of tetrodotoxin-insensitive Na+ channels in neurons of rat dorsal root ganglia.
    J Membr Biol. 1992 Jul;129(1):71-80 PMID: 1328647
  14. Sodium currents in smooth muscle cells freshly isolated from stomach fundus of the rat and ureter of the guinea-pig.
    J Physiol. 1991 Oct;442:351-75 PMID: 1665861
  15. Voltage-dependent sodium and potassium channels in mammalian cultured Schwann cells.
    Proc Natl Acad Sci U S A. 1985 Feb;82(3):948-52 PMID: 2579384
  16. Action potential and non-linear current-voltage relation in starfish oocytes.
    J Physiol. 1975 Mar;246(1):37-54 PMID: 1169319
  17. Development of excitability in embryonic chick skeletal muscle cells.
    J Cell Physiol. 1975 Dec;86(3 Pt 1):503-10 PMID: 1202030
  18. Sodium and calcium components of the action potential in a developing skeletal muscle cell line.
    J Physiol. 1975 Jan;244(1):145-59 PMID: 1168257
  19. The presence of voltage-gated sodium, potassium and chloride channels in rat cultured astrocytes.
    Proc R Soc Lond B Biol Sci. 1985 Sep 23;225(1240):299-313 PMID: 2414778
  20. Tetrodotoxin, saxitoxin, and the molecular biology of the sodium channel.
    Ann N Y Acad Sci. 1986;479:1-445 PMID: 2433985
  21. Studies on sensory neurons of the mouse with intracellular-recording and horseradish peroxidase-injection techniques.
    J Neurophysiol. 1979 Jul;42(4):1134-45 PMID: 479922
  22. Sodium currents during differentiation in a human neuroblastoma cell line.
    J Gen Physiol. 1991 Mar;97(3):521-39 PMID: 1645394
  23. Sodium currents in axon-associated Schwann cells from adult rabbits.
    J Physiol. 1987 May;386:181-203 PMID: 2445963
  24. Calcium currents in aged rat dorsal root ganglion neurones.
    J Physiol. 1993 Feb;461:467-83 PMID: 8394426
  25. Differential modulation of TTX-sensitive and TTX-resistant Na+ channels in spinal cord astrocytes following activation of protein kinase C.
    J Neurosci. 1993 Nov;13(11):4889-97 PMID: 8229203
  26. Kinetic analysis of two types of Na+ channels in rat dorsal root ganglia.
    J Physiol. 1993 Jul;466:9-37 PMID: 8410717
  27. Development of action potentials in a clonal rat skeletal muscle cell line.
    Nat New Biol. 1973 Jan 31;241(109):158-9 PMID: 4512622
  28. Ontogenic development of the TTX-sensitive and TTX-insensitive Na+ channels in neurons of the rat dorsal root ganglia.
    Brain Res Dev Brain Res. 1992 Jan 17;65(1):93-100 PMID: 1312915
  29. Evidence for two transient sodium currents in the frog node of Ranvier.
    J Physiol. 1985 Apr;361:339-60 PMID: 2580980
  30. Properties of toxin-resistant sodium channels produced by chemical modification in frog skeletal muscle.
    J Physiol. 1980 Aug;305:485-500 PMID: 6255148
  31. Na and Ca spikes produced by ions passing through Ca channels in mouse ovarian oocytes.
    Pflugers Arch. 1982 Oct;395(1):84-6 PMID: 6294589
  32. Existence of distinct sodium channel messenger RNAs in rat brain.
    Nature. 1986 Mar 13-19;320(6058):188-92 PMID: 3754035
  33. TARICHATOXIN--TETRODOTOXIN: A POTENT NEUROTOXIN.
    Science. 1964 May 29;144(3622):1100-10 PMID: 14148429
  34. Neurotoxins that act on voltage-sensitive sodium channels in excitable membranes.
    Annu Rev Pharmacol Toxicol. 1980;20:15-43 PMID: 6247957
  35. A molecular view of neurotransmitter receptors and ionic channels.
    Harvey Lect. 1987-1988;83:121-65 PMID: 2469666
  36. A monoclonal antibody against neurofilament protein specifically labels a subpopulation of rat sensory neurones.
    J Comp Neurol. 1984 Sep 10;228(2):263-72 PMID: 6434599
  37. Large and small vertebrate sensory neurons express different Na and K channel subtypes.
    Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9569-73 PMID: 1329102
  38. A Ca- dependent regenerative response in rodent dorsal root ganglion cells cultured in vitro.
    Brain Res. 1976 Oct 15;115(2):334-8 PMID: 974750
  39. Three types of sodium channels in adult rat dorsal root ganglion neurons.
    Brain Res. 1992 Oct 2;592(1-2):283-97 PMID: 1280518
  40. Mechanism of action of oxytocin in rat vagal neurones: induction of a sustained sodium-dependent current.
    J Physiol. 1992 Nov;457:131-42 PMID: 1297830
  41. Electrical properties of rat dorsal root ganglion neurones with different peripheral nerve conduction velocities.
    J Physiol. 1985 Feb;359:47-63 PMID: 2987489
  42. The chemistry of tetrodotoxin.
    Ann N Y Acad Sci. 1986;479:32-43 PMID: 3468846
  43. Neurotensin induces an inward current in rat mesencephalic dopaminergic neurons.
    Neurosci Lett. 1993 Apr 30;153(2):192-6 PMID: 7687049
  44. Action potentials dependent on monovalent cations in developing mouse embryos.
    Dev Biol. 1985 Jul;110(1):200-6 PMID: 2408941
  45. The action potential of chick dorsal root ganglion neurones maintained in cell culture.
    J Physiol. 1977 May;267(2):281-98 PMID: 559758
  46. Ionic mechanisms of electrical excitability in rat sensory neurons during postnatal ontogenesis.
    Neuroscience. 1991;41(1):303-9 PMID: 1647504
  47. Properties of visceral primary afferent neurons in the nodose ganglion of the rabbit.
    J Neurophysiol. 1985 Aug;54(2):245-60 PMID: 4031986
  48. Pharmacological studies on tarichatoxin, a potent neurotoxin.
    J Pharmacol Exp Ther. 1963 Apr;140:31-40 PMID: 13962288
  49. Tetrodotoxin-sensitive voltage-dependent Na currents recorded from Xenopus oocytes injected with mammalian cardiac muscle RNA.
    Brain Res. 1988 Apr;427(2):187-91 PMID: 2454698
  50. Transfection of activated ras into an excitable cell line (AtT-20) alters tetrodotoxin sensitivity of voltage-dependent sodium current.
    Pflugers Arch. 1990 Apr;416(1-2):120-5 PMID: 2191273
  51. Spontaneous discharges caused by increasing external Na ion or divalent cation concentration in the mouse dorsal root ganglion cells in culture.
    Brain Res. 1980 Sep 8;196(2):560-4 PMID: 6249453
  52. Regulation of muscle sodium channel transcripts during development and in response to denervation.
    Dev Biol. 1990 Dec;142(2):360-7 PMID: 2175278
  53. Electrophysiological studies of new-born rat nodose neurones in cell culture.
    J Physiol. 1982 Mar;324:429-39 PMID: 6284921
  54. Apamin, a highly potent blocker of the TTX- and Mn2(+)-insensitive fast transient Na+ current in young embryonic heart.
    J Mol Cell Cardiol. 1991 Jan;23(1):25-39 PMID: 2038068
  55. Tissue-specific expression of the voltage-sensitive sodium channel.
    J Membr Biol. 1992 Feb;125(3):193-205 PMID: 1313507
  56. Tetrodotoxin binding as a marker for functional differentiation of various brain regions during chick and mouse development.
    J Neurochem. 1975 Feb;24(2):261-70 PMID: 1113104
  57. Ion channels in development.
    Annu Rev Neurosci. 1979;2:363-97 PMID: 395884
  58. Tetrodotoxin.
    Trends Biochem Sci. 1988 Mar;13(3):76-7 PMID: 3245066
  59. A single point mutation confers tetrodotoxin and saxitoxin insensitivity on the sodium channel II.
    FEBS Lett. 1989 Dec 18;259(1):213-6 PMID: 2557243
  60. Charge movement associated with the opening and closing of the activation gates of the Na channels.
    J Gen Physiol. 1974 May;63(5):533-52 PMID: 4824995
  61. A role for action potentials in maturing Rana pipiens oocytes.
    Dev Biol. 1983 Jul;98(1):60-9 PMID: 6305748
  62. The ionic basis of action potentials in petrosal ganglion cells of the cat.
    J Physiol. 1983 Sep;342:591-602 PMID: 6631750
  63. Sodium currents in dissociated bull-frog sympathetic neurones.
    J Physiol. 1987 Aug;389:605-27 PMID: 2445980
  64. A mutant of TTX-resistant cardiac sodium channels with TTX-sensitive properties.
    Science. 1992 May 22;256(5060):1202-5 PMID: 1375397
  65. TTX-sensitive and TTX-insensitive sodium channel mRNA transcripts are independently regulated in adult skeletal muscle after denervation.
    Neuron. 1991 Sep;7(3):421-7 PMID: 1654949
  66. The binding of saxitoxin and tetrodotoxin to excitable tissue.
    Rev Physiol Biochem Pharmacol. 1977;79:1-50 PMID: 335473
  67. Structure and function of voltage-sensitive ion channels.
    Science. 1988 Oct 7;242(4875):50-61 PMID: 2459775
  68. Chemicals as tools in the study of excitable membranes.
    Physiol Rev. 1974 Oct;54(4):813-89 PMID: 4153804
  69. Structural and developmental differences between three types of Na channels in dorsal root ganglion cells of newborn rats.
    J Membr Biol. 1990 Jun;116(2):117-28 PMID: 2166163
  70. Characterization of TTX-sensitive and TTX-resistant sodium currents in small cells from adult rat dorsal root ganglia.
    J Physiol. 1993 Apr;463:39-56 PMID: 8246189
  71. Molecular diversity of voltage-sensitive Na channels.
    Annu Rev Physiol. 1989;51:401-18 PMID: 2540698
  72. Mapping the site of block by tetrodotoxin and saxitoxin of sodium channel II.
    FEBS Lett. 1991 Nov 18;293(1-2):93-6 PMID: 1660007
  73. Tetrodotoxin-resistant sodium current of rat nodose neurones: monovalent cation selectivity and divalent cation block.
    J Physiol. 1987 Aug;389:255-70 PMID: 2445974
  74. Development of sensitivity to tetrodotoxin of chick embryonic hearts with age.
    J Mol Cell Cardiol. 1971 Dec;3(3):271-86 PMID: 5293984
  75. Primary structure of Electrophorus electricus sodium channel deduced from cDNA sequence.
    Nature. 1984 Nov 8-14;312(5990):121-7 PMID: 6209577
  76. Tetrodotoxin-resistant sodium and calcium components of action potentials in dorsal root ganglion cells of the adult mouse.
    J Neurophysiol. 1978 Sep;41(5):1096-1106 PMID: 702189
  77. Electrical excitability in the egg cell membrane of the tunicate.
    J Physiol. 1974 Apr;238(1):37-54 PMID: 4857991
  78. Tetrodotoxin sensitivity and Ca component of action potentials of mouse dorsal root ganglion cells cultured in vitro.
    Brain Res. 1978 Oct 6;154(1):69-82 PMID: 698823
  79. Diversity of sodium channels in adult and cultured cells, in oocytes and in lipid bilayers.
    Rev Physiol Biochem Pharmacol. 1990;115:1-49 PMID: 2158141
  80. Functional differences between two classes of sodium channels in developing rat skeletal muscle.
    Science. 1986 Jul 18;233(4761):361-4 PMID: 2425432
  81. Sodium current in single rat heart muscle cells.
    J Physiol. 1981 Sep;318:479-500 PMID: 7320902
  82. Ionic determinants of excitability in cultured mouse dorsal root ganglion and spinal cord cells.
    Brain Res. 1977 Nov 18;136(3):445-53 PMID: 922495
  83. TETRODOTOXIN BLOCKAGE OF SODIUM CONDUCTANCE INCREASE IN LOBSTER GIANT AXONS.
    J Gen Physiol. 1964 May;47:965-74 PMID: 14155438
  84. Single-channel current/voltage relationships of two kinds of Na+ channel in vertebrate sensory neurons.
    Pflugers Arch. 1993 Jun;423(5-6):492-6 PMID: 8394570
  85. Voltage-clamp experiments in normal and denervated mammalian skeletal muscle fibres.
    J Physiol. 1980 Sep;306:377-410 PMID: 6257898
  86. Tetrodotoxin desensitization in aggregates of embryonic chick heart cells.
    J Gen Physiol. 1973 Sep;62(3):286-302 PMID: 4730668
  87. Primary structure and expression of a sodium channel characteristic of denervated and immature rat skeletal muscle.
    Neuron. 1990 Feb;4(2):233-42 PMID: 2155010
  88. Effects of alkaline earth cations (Ca, Sr, Ba) on cultured spinal neurons of the mouse. A light and electron microscopic study.
    Brain Res. 1979 Sep 7;173(1):168-73 PMID: 487081
  89. Calcium channel characteristics conferred on the sodium channel by single mutations.
    Nature. 1992 Apr 2;356(6368):441-3 PMID: 1313551
  90. Effects of Ca2+ antagonists and antiepileptics on tetrodotoxin-sensitive Ca(2+)-conducting channels in isolated rat hippocampal CA1 neurons.
    Neurosci Lett. 1992 Dec 14;148(1-2):60-2 PMID: 1338651
  91. Bullfrog dorsal root ganglion cells having tetrodotoxin-resistant spikes are endowed with nicotinic receptors.
    J Neurophysiol. 1989 Sep;62(3):657-64 PMID: 2788718
  92. Development of anomalous rectification (Ih) and of a tetrodotoxin-resistant sodium current in embryonic quail neurones.
    J Physiol. 1991 Oct;442:127-45 PMID: 1798027
  93. Changes in sodium channels during neural differentiation in the isolated blastomere of the ascidian embryo.
    J Physiol. 1990 Dec;431:39-74 PMID: 1966050
  94. Voltage clamp analysis of tetrodotoxin-sensitive and -insensitive sodium channels in rat muscle cells developing in vitro.
    J Neurosci. 1985 Sep;5(9):2559-64 PMID: 2411888
  95. Resting and spike potentials of skeletal muscle fibres of salt-water elasmobranch and teleost fish.
    J Physiol. 1967 Jun;190(3):499-518 PMID: 6051784
  96. Tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels in tissue-cultured spinal ganglion neurons from adult mammals.
    Brain Res. 1980 Jan 20;182(1):191-7 PMID: 7350989
  97. Sodium dependent tetrodotoxin-resistant action potentials in a leech neuron.
    Brain Res. 1976 Feb 6;102(2):368-73 PMID: 1247893
  98. Ion channels in vertebrate glia.
    Annu Rev Neurosci. 1990;13:441-74 PMID: 2158266
  99. Tetrodotoxin-sensitive calcium-conducting channels in the rat hippocampal CA1 region.
    J Physiol. 1992 May;450:529-46 PMID: 1331428
  100. Patch-clamp study of the tetrodotoxin-resistant sodium current in group C sensory neurones.
    Neurosci Lett. 1984 Oct 12;51(2):241-6 PMID: 6096775
  101. Na+ and Ca2+ currents of acutely isolated adult rat nodose ganglion cells.
    J Neurophysiol. 1986 Mar;55(3):527-39 PMID: 2420945
  102. Tetrodotoxin, saxitoxin and their significance in the study of excitation phenomena.
    Pharmacol Rev. 1966 Jun;18(2):997-1049 PMID: 5328391
  103. Calcium- and sodium-dependent action potentials of mouse spinal cord and dorsal root ganglion neurons in cell culture.
    J Neurophysiol. 1982 Apr;47(4):641-55 PMID: 7069458
  104. The influence of capsaicin on membrane currents in dorsal root ganglion neurones of guinea-pig and chicken.
    Pflugers Arch. 1987 Aug;409(4-5):403-10 PMID: 2442708
  105. Distribution of tetrodotoxin in the tissues of the flatworm Planocera multitentaculata (Platyhelminthes).
    Toxicon. 1987;25(9):975-80 PMID: 3433307
  106. Kinetics of drug action and equilibrium results at the node of Ranvier.
    Physiol Rev. 1981 Oct;61(4):785-828 PMID: 6270710
  107. Probing the molecular structure of the voltage-dependent sodium channel.
    Annu Rev Neurosci. 1988;11:455-95 PMID: 2452597
  108. Studies on tetrodotoxin resistant action potentials in denervated skeletal muscle.
    Acta Physiol Scand. 1971 Nov;83(3):382-8 PMID: 5134176
  109. Conduction velocity is related to morphological cell type in rat dorsal root ganglion neurones.
    J Physiol. 1985 Feb;359:31-46 PMID: 3999040
  110. Occurrence of tetrodotoxin and anhydrotetrodotoxin in Vibrio sp. isolated from the intestines of a xanthid crab, Atergatis floridus.
    J Biochem. 1986 Jan;99(1):311-4 PMID: 3754255
  111. Ionic currents through the membrane of the mammalian oocyte and their comparison with those in the tunicate and sea urchin.
    J Physiol. 1977 May;267(2):465-95 PMID: 559759
  112. Electrophysiology of parasympathetic neurones isolated from the interatrial septum of bull-frog heart.
    J Physiol. 1990 Aug;427:89-125 PMID: 2213612
  113. Ionic currents in the somatic membrane of rat dorsal root ganglion neurons-I. Sodium currents.
    Neuroscience. 1981;6(12):2423-30 PMID: 6275294
  114. Subtypes of dorsal root ganglion neurons based on different inward currents as measured by whole-cell voltage clamp.
    Mol Cell Biochem. 1988 Mar-Apr;80(1-2):95-107 PMID: 3173341
  115. TTX-sensitive action potentials and excitability of adult rat sensory neurons cultured in serum- and exogenous nerve growth factor-free medium.
    Neurosci Lett. 1991 Jan 2;121(1-2):88-92 PMID: 2020393
  116. Characterization of sodium currents in mammalian sensory neurons cultured in serum-free defined medium with and without nerve growth factor.
    J Membr Biol. 1990 Apr;115(1):13-29 PMID: 2159518
  117. Ionic differences between somatic and axonal action potentials in snail giant neurones.
    J Physiol. 1972 Jan;220(2):267-81 PMID: 5014099
  118. Membrane currents of the tunicate egg under the voltage-clamp condition.
    J Physiol. 1976 Jan;254(3):607-38 PMID: 943522
  119. Differential properties of tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels in rat dorsal root ganglion neurons.
    J Neurosci. 1992 Jun;12(6):2104-11 PMID: 1318956
Article Info
Journal
Cellular and molecular neurobiology
Abbr.
Cell Mol Neurobiol
ISSN
0272-4340
DOI
10.1007/BF02088322
Published
1994-06-00
Pages
227-44
Language
English
Region
United States
NLM ID
8200709
Subset
IM
External Links
PubMed source DOI: 10.1007/BF02088322 View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2